Important Differences Research Articles

Obesity Does Not Negatively Affect Patient-perceived Outcomes After Cervical Disc Replacement for Disc Herniation.

Retrospective review. To assess the impact of Body Mass Index (BMI) on patient-reported outcome measures (PROMs) after cervical disc replacement (CDR). BMI may affect PROMs after spine surgery. Primary CDR recipients for herniated disc(s) with BMI <40 were retrospectively selected from a single-surgeon registry. Cohorts were divided into non-obese (BMI <30) and obese (BMI ≥30). Intercohort in-hospital complication rates were compared through independent samples t tests. Pre/postoperative PROMs were compared between cohorts through multivariable regression accounting for demographic differences. Final follow-up dates between patients averaged 11.8 ± 9.3 months. PROMs assessed included Patient-reported Outcomes Measurement Information System-Physical Function, Neck Disability Index, Visual Analog Scale-Neck, Visual Analog Scale-Arm, and the 9-item Patient Health Questionnaire. Improvements in PROMs were evaluated and compared at each follow-up within cohorts through paired t tests. The magnitude of improvement in PROMs from preoperative baseline at 6-week follow-up (∆PROM-6W) and final follow-up (∆PROM-FF) along with achievement rates of minimum clinically important differences were compared between cohorts through multivariable regression accounting for demographic differences. Of 153 patients, 53 patients were noted as obese. Demographic differences included age, prevalence of hypertension and diabetes, and comorbidity burden scores ( P ≤ 0.011, all). No significant variations in in-hospital complications were found. The non-obese cohort demonstrated improvements in all PROMs at 6 weeks and final follow-up periods ( P ≤ 0.005, all). The obese cohort demonstrated improvements in all postoperative PROMs besides 9-item Patient Health Questionnaire at 6 weeks ( P ≤ 0.015, all). After accounting for age and comorbidity variations, there were no significant intercohort differences in raw PROM scores, ∆PROM-6W, ∆PROM-FF, or minimum clinically important difference achievement rates. Regardless of BMI, patients experience significant improvements in physical function, disability, pain, and mental health after CDR for disc herniation. Patients with obesity do not suffer inferior patient-perceived outcomes after CDR. These findings may help surgeons counsel patients in the preoperative period.

Deep Peroneal Neurectomy for Midfoot Arthritis: A Comprehensive Review, Surgical Technique, and Case Series

Patients with painful midfoot arthritis unsuccessfully treated with conservative measures have been historically left with the surgical option of midfoot arthrodesis as a definitive treatment. In recent years, excision of the deep peroneal nerve has been offered as a potential alternative. Existing literature on the outcomes of patients undergoing deep peroneal neurectomy for the treatment of midfoot arthritis is limited and piecemeal. In this comprehensive review, technique guide, and retrospective case series, we consolidate the evidence around deep peroneal neurectomy for midfoot arthritis, review operative technique, and determine the outcomes of 4 patients who underwent deep peroneal neurectomy from February 2021 to December 2022 using Patient-Reported Outcome Measurement Information System Physical Function and Pain Interference scores. Four original articles from National Center for Biotechnology Information Medline, published through May 2023, were included. The outcomes of patients treated with deep peroneal neurectomy for midfoot arthritis are discussed. In our case series, the average amount of time between surgery and final postoperative Patient-Reported Outcome Measurement Information System scores was 289 days. The average preoperative physical function score was 36.8. Three patients showed a minimal clinically important difference in physical function; postoperative average was 41.3. Three patients had a minimally clinical important reduction in pain levels (average preoperative pain interference score was 65.8; average postoperative pain interference score was 59.3). One patient underwent a revision neurectomy for inadequate pain relief, and another sought additional treatment for inadequate pain relief. All patients returned to walking in a shoe within 1 month. The outcomes of our case series are similar to those of previously published case series, which demonstrate satisfactory results and acceptable complication rates. For patients with symptomatic midfoot arthritis, deep peroneal neurectomy can be an effective treatment option to reduce pain and improve physical function while requiring minimal postoperative recovery time.

A global set of barley varieties shows a high diversity in starch structural properties and related gelatinisation characteristics

The gelatinisation temperature and bimodal granule size distribution of barley starch are important characteristics regarding resource efficiency and product quality in the brewing industry. In this work, the diversity in starch amylose content and granule proportions in a set of modern barley varieties (N = 23) was investigated and correlated with their starch gelatinisation behaviour. Milled barley samples had peak starch gelatinisation temperatures ranging from 60.1 to 66.5 °C. Upon separating the barley starch from the non-starch compounds, sample-dependent decreases in starch gelatinisation temperatures were observed, indicating the importance of differences in barley composition. The peak gelatinisation temperatures of milled barley and isolated barley starches were strongly correlated (r = 0.96), indicating that the behaviour of the starch population is strongly reflected in the measurements performed on milled barley. Therefore, we investigated whether amylose content or starch granule size distribution could predict the gelatinisation behaviour of the starches. Broad ranges in the small starch granule volumes (13.9–32.0 v/v%) and amylose contents (18.2–30.7 w/w%) of the barley starches were observed. For the barley samples collected in the north of the USA (N = 8), the small starch granule volumes correlated positively with the peak gelatinisation temperatures of barley starches (r = 0.90, p < 0.01). The considerable variation in starch properties described in this work highlights that, besides starch content, starch gelatinisation temperature or granule size distribution might provide brewers with useful information to optimise resource efficiency.

Deconstructing Fears of Terrorism: A Comparison between Fear from Domestic and International Terrorist Groups

ABSTRACT Although research on fears of terrorism has been growing, previous studies approached the topic of the fear of terrorism as a monolithic concept without considering the various political aspects of terrorism as a crime. The current research employed a novel approach to studying the fear of terrorism as a polylithic phenomenon by comparing three different types of fears of terrorism among Americans: general fears of terrorism, fears of domestic terrorist groups, and fears of international terrorist groups. Drawing on a nationally representative sample from the Chapman Survey of American Fears, Wave 5 (2018), the results of the analysis indicated that the predictors were differentially associated with the three types of fear with respect to their statistical significance and correlation directions. Thus, this study provides a significant contribution to the literature on the fear of terrorism topic by illustrating the important differences among general fears of terrorism, fears of domestic terrorist groups, and fears of international terrorist groups.

Lecanemab Questions.

The recently published results of the 18-month randomized controlled trial of lecanemab, reporting the efficacy of the drug in slowing the progression of early Alzheimer disease, quickly led to approval by the FDA and widespread acceptance of lecanemab treatment. However, there are a number of matters that deserve further consideration. The success of blinding was not assessed, even as infusion reactions and the cerebral pathology underlying amyloid-related imaging abnormalities could have signaled to many participants that they were on drug, potentially exerting a potent placebo effect. The value of the outcome to participants is not defined in the absolute terms necessary for clinical decision-making, and the difference attributable to lecanemab was between 18% and 46% of estimates of the minimal clinically important difference on the Clinical Dementia Rating Scale Sum of Boxes. The attenuation of change on the Alzheimer's Disease Assessment Scale-Cognitive 14 achieved by lecanemab at 18 months was 50% of that achieved by donepezil at 6 months. Lecanemab treatment imposes a high treatment burden. The fact that the burden commences at the initiation of lecanemab treatment, whereas the benefit accrues years later requires us to take into account value discounting over time, which would significantly reduce the benefit/burden ratio. Finally, treatment with monoclonal antibodies to cerebral amyloid has consistently been associated with progressive cerebral atrophy. At the least, these issues should be raised in treatment discussions with patients. They also suggest a need to very seriously reconsider how we evaluate clinical trial results preparatory to translating them into clinical practice. Some suggestions are provided.

South Cuidrach

A new site in north Skye has revealed evidence of human occupation from the Late Upper Palaeolithic as well as the Early and Late Mesolithic periods, suggesting repeated visits by humans for at least 5,000 years from the Late Glacial Interstadial through the Loch Lomond Readvance and up to the mid-Holocene, a time of dynamic climatic and sea-level change. South Cuidrach is one of several sites in the north of the Isle of Skye and around the Inner Sound with lithic (stone tool) evidence diagnostic of a human presence before the mid-Holocene. These sites currently represent a unique concentration of pre-Late Mesolithic sites in Scotland. The lithic evidence which forms the backbone of the cultural and temporal characterisation of the site at South Cuidrach is outlined here. This includes characteristic points and microliths, burins, cores and other items diagnostic of specific cultural groups. Additionally, it has become evident that Rum bloodstone, a raw material well known from the Late Mesolithic period in the region, may be absent before the Early/Late Mesolithic transition, with baked mudstone from Staffin in North Skye being the primary raw material used before this time. The need for detailed knowledge of the region’s lithic technology and typology is well illustrated here, as small details frequently reflect important chronological differences.

1081 Risk Factors for Long Term Opioid Use After Elective Lumbar Spine Surgery: A MSSIC Study

INTRODUCTION: Long-term opioid use after elective lumbar spine surgery is a significant concern, given the current opioid epidemic and its impact on public health. Identifying risk factors for long-term opioid use after spine surgery is crucial in developing effective interventions to reduce the incidence of opioid dependence in this patient population. METHODS: A retrospective analysis of patient data was conducted using the Michigan Spine Surgery Improvement Collaborative (MSSIC) registry. Patients who underwent elective lumbar spine surgery between March 2018, and September 2021, were included, resulting in a total of 3599 patients at one year and 966 patients at two years follow-up. Poisson generalized estimating equation models were used for multivariate analyses. RESULTS: A total of 493 (13.7%) and 137 (14.2%) patients were still using opiates at one-year and two-years post-surgery respectively. Discharge morphine milligram equivalents (MMEs), baseline PROMIS PF functional scores, baseline pain scores, age, gender, education level, pre-operative opioid use, and not achieving the minimal clinically important difference (MCID) in PROMIS PF scores at follow-up were significantly associated with long-term opioid use. Specifically, pre-operative opioid use had the strongest association with opioid use at one year (IRR = 2.83, CI: 2.40-3.34, p &lt; 0.001) and two years (IRR = 3.79, CI: 2.53-5.68, p &lt; 0.001). Additionally, not achieving MCID in PROMIS scores at follow-up was strongly associated (IRR = 2.00, CI: 1.72-2.32, p &lt; 0.001 and IRR = 2.18, CI: 1.64-2.91, p &lt; 0.001) with opioid use at both time points (1-year and 2-year respectively). CONCLUSIONS: Pre-operative opioid use and not achieving MCID in PROMIS scores at follow-up were the strongest predictors of long-term opioid use after elective lumbar spine surgery. Identifying these risk factors can help clinicians target interventions to reduce opioid use in at-risk patients and improve postoperative outcomes.

Predicting effects of a digital stress intervention for patients with depressive symptoms: Development and validation of meta-analytic prognostic models using individual participant data.

Digital stress interventions could be helpful as an "indirect" treatment for depression, but it remains unclear for whom this is a viable option. In this study, we developed models predicting individualized benefits of a digital stress intervention on depressive symptoms at 6-month follow-up. Data of N = 1,525 patients with depressive symptoms (Center for Epidemiological Studies' Depression Scale, CES-D ≥ 16) from k = 6 randomized trials (digital stress intervention vs. waitlist) were collected. Prognostic models were developed using multilevel least absolute shrinkage and selection operator and boosting algorithms, and were validated using bootstrap bias correction and internal-external cross-validation. Subsequently, expected effects among those with and without a treatment recommendation were estimated based on clinically derived treatment assignment cut points. Performances ranged from R² = 21.0%-23.4%, decreasing only slightly after model optimism correction (R² = 17.0%-19.6%). Predictions were greatly improved by including an interim assessment of depressive symptoms (optimism-corrected R2 = 32.6%-35.6%). Using a minimally important difference of d = -0.24 as assignment cut point, approximately 84.6%-93.3% of patients are helped by this type of intervention, while the remaining 6.7%-15.4% would experience clinically negligible benefits (δ^ = -0.02 to -0.19). Using reliable change as cut point, a smaller subset (39.3%-46.2%) with substantial expected benefits (δ^ = -0.68) receives a treatment recommendation. Meta-analytic prognostic models applied to individual participant data can be used to predict differential benefits of a digital stress intervention as an indirect treatment for depression. While most patients seem to benefit, the developed models could be helpful as a screening tool to identify those for whom a more intensive depression treatment is needed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Role of Multilevel Intercostal Nerve Block in Local Anesthetic Thoracoscopy.

Intercostal nerve block (ICNB) has long been used in thoracic surgery. Local anesthetic thoracoscopy (LAT) is performed under conscious sedation with local anesthesia at the port insertion site. This alone, however, does not anesthetize the parietal pleura from where biopsies are taken and patients can experience pain. To compare LAT with multilevel ICNB versus standard care to determine whether it reduces pain during and post-LAT, its effect on analgesia use, the hospital length of stay (LOS), and related complications. Prospective analysis of patients undergoing LAT between January and June 2021. In the ICNB group, levobupivacaine/xylocaine is administered at the angle of the rib immediately before LAT (up to 5 rib spaces). Visual Analog Score for pain (0 to 100mm) was measured at 1 and 2 hours post-LAT and daily including analgesia use. Twenty patients (10 ICNB vs. 10 standard care group). The mean age is 68 years with 70% males. Visual Analog Score for pain in the ICNB group reduced by 55mm at 1 and 2 hours post-LAT and 45mm at day 1 ( P <0.05) (minimal clinically important difference >16mm]. Median LOS was reduced by 50% in the ICNB group ( P <0.05). Paracetamol use reduced by 56% ( P <0.05). ICNB not only significantly reduces postprocedure pain but also reduces LOS.

Smokers Achieved Minimal Clinically Important Difference for Visual Analog Scale and American Shoulder and Elbow Surgeons Scores at a Lower Rate Than Nonsmokers Even When Repaired Supraspinatus Tendons Were Intact on Postoperative Magnetic Resonance Imaging

To investigate the impact of smoking on clinical outcomes after repair of supraspinatus tendon in patients who had an intact repair found on postoperative magnetic resonance imaging. Patients who received primary complete repair of supraspinatus tendon tear between 2014 and 2020 were retrospectively identified. Patients were excluded if a postoperative magnetic resonance imaging scan was not available or if the follow-up was less than 2 years. Visual analog score (VAS), American Shoulder and Elbow Surgeons (ASES) score, and active forward flexion were assessed at the 2-year follow-up. The percentage of patients acquiring minimal clinically important difference (MCID) was reported. One hundred primary supraspinatus tendon repairs were included. The healing rate was 77% in smokers and 90% in nonsmokers. Smoking was the independent predictor of a poorer 2-year VAS (P < .001) and ASES (P < .001) scores. Significant improvement in clinical outcomes was observed between preoperation and the 2-year follow-up, regardless of the integrity of the repair or smoking status (P < .001). When the repaired tendon was intact, nonsmokers had a greater chance of achieving MCID in 2-year VAS and ASES scores than smokers. Ninety-nine percent of nonsmokers, compared with 82% of smokers, achieved MCID in VAS at the 2-year follow-up (P= .023). The corresponding figures for ASES were 98% and 71%, respectively (P= .004). In this study, smoking was associated with poorer clinical outcomes, including a greater 2-year VAS pain score and a lower 2-year ASES score, when compared with nonsmokers, even in cases in which there was no full-thickness retear of the repaired supraspinatus tendon. Level III, retrospective cohort study.

281 Does Smoking Status Affect Achievement of Satisfaction and Minimum Clinically Important Difference in Outcomes in Patients With Cervical Myelopathy at 24 Months? A QOD Study

INTRODUCTION: It is not clear whether smoking impacts patient-reported outcomes (PROs) in patients with cervical spondylotic myelopathy (CSM). METHODS: This was an analysis of the prospective Quality Outcomes Database CSM module. Patients of age = 18 years diagnosed with primary CSM who underwent elective surgery were included. PROs (VAS neck and arm pain, NDI, mJOA, EQ-5D, and NASS patient satisfaction) were collected at baseline and 24 months. RESULTS: Of the 1,141 patients with CSM, 202 (17.7%) were smokers and 939 (82.3%) were non-smokers. Compared to the non-smokers, smokers were younger (56.3 ± 11.3 vs 61.5 ± 11.7, p&lt;0.01) and had lower BMI (29.3 ± 6.8 vs 30.3 ± 6.3, p=0.04). A higher number of smokers had depression, anxiety, and COPD (all p&lt;0.01). At baseline, smokers had worse pain (neck: 6.0 ± 3.2 vs 5.1 ± 3.3; arm: 5.7 ± 3.2 vs 4.7 ± 3.5), disability (NDI: 45.2 ± 20.0 vs 37.1 ± 20.6), myelopathy (mJOA: 11.5 ± 2.9 vs 12.2 ± 2.8), and quality of life (EQ-5D: 0.51 ± 0.23 vs 0.57 ± 0.22) (all p &lt; 0.01). At 24-month follow-up, a higher proportion of smokers achieved MCID in mJOA (69.4% vs 56.6%, p &lt; 0.01) compared to non-smokers. Otherwise, there was no significant difference in the PROs at 24-month follow-up between the two groups (all p &gt; 0.05). The two groups were also similarly satisfied (NASS 1-2: smoker 81.2% vs non-smoker 84.6%, p = 0.29) 24 months after surgery. CONCLUSIONS: Despite smokers having worse baseline characteristics in terms of comorbidities and outcomes of interest, both smokers and non-smokers experienced improvement in all the PROs and achieved similar rates of MCID and satisfaction. Although smoking continues to be an important risk factor for poor surgical outcome, it may not have significant impact on PROs and satisfaction in this patient population.

Diverse learners: learning disabilities and quality of life following mind-body and health education interventions for adults with neurofibromatosis.

Neurofibromatosis (NF) is associated with low quality-of-life (QoL). Learning disabilities are prevalent among those with NF, further worsening QoL and potentially impacting benefits from mind-body and educational interventions, yet research on this population is scarce. Here, we address this gap by comparing NF patients with and without learning disabilities on QoL at baseline and QoL-related gains following two interventions. Secondary analysis of a fully-powered RCT of a mind-body program (Relaxation Response Resiliency Program for NF; 3RP-NF) versus an educational program (Health Enhancement Program for NF; HEP-NF) among 228 adults with NF. Participants reported QoL in four domains (Physical Health, Psychological, Social Relationships, and Environmental). We compare data at baseline, post-treatment, and 12-month follow-up, controlling for intervention type. At baseline, individuals with NF and learning disabilities had lower Psychological (T = -3.0, p = .001) and Environmental (T = -3.8, p < .001) QoL compared to those without learning disabilities. Both programs significantly improved all QoL domains (ps < .0001-0.002) from baseline to post-treatment, regardless of learning disability status. However, those with learning disabilities exceeded the minimal clinically important difference in only one domain (Psychological QoL) compared to three domains in individuals without learning disabilities. Moreover, those with learning disabilities failed to sustain statistically significant gains in Psychological QoL at 12-months, while those without learning disabilities sustained all gains. Adults with NF and learning disabilities have lower Psychological and Environmental QoL. While interventions show promise in improving QoL regardless of learning disabilities, additional measures may bolster clinical benefit and sustainability among those with learning disabilities.

Do policy actors have different views of what constitutes evidence in policymaking?

The role played by evidence in policymaking is hotly disputed and there is no agreement over how evidence is defined. This article examines whether policy actors have different views of what counts as evidence and which factors influence these perceptions (for example, professional background, length of service, organisation setting, cultures of evidence)? In addressing this question, we contribute to the growing research focus on the context of evidence use. Q methodology – a mixed method approach to study people’s attitudes towards a topic – is used in interviewing 67 policy actors and comparing two countries, Scotland and Wales, to find out whether there are different cultures of evidence. In both countries, we identified four distinct profiles of attitudes towards evidence: the evidence-based policymaking (EBPM) Idealist, the Pragmatist, the Inclusive, and the Political. Our research highlights important differences between the two contexts, with a greater leaning towards EBPM views of evidence in Wales, and more pragmatism in defining evidence in Scotland. We illustrate how different cultures of evidence coexist in a same context and highlight their similarities and differences. We also contribute to the understanding of the value of Q methodology research by showing that it can be used to compare two datasets collected in different countries.

Influence of Concomitant Meniscal Allograft Transplantation on Midterm Outcomes After Osteochondral Allograft Transplantation: A Comparative Matched-Pair Analysis.

Osteochondral allograft transplantation (OCAT) is an accepted knee joint-preserving treatment strategy for focal osteochondral lesions that is often conducted in combination with meniscal allograft transplantation (MAT). Despite its frequent and simultaneous utilization, there remains a lack in the literature reporting on outcomes and failure rates after concomitant procedures. To determine (1) the midterm clinical success rate after OCAT+MAT in comparison with a matched-pair cohort undergoing isolated OCAT, (2) whether patient-specific and procedural variables influence the risk of failure, and (3) patient-reported outcome measures over time. Cohort study; Level of evidence, 3. A single-center matched-pair cohort study was conducted investigating outcomes in patients who underwent OCAT of the medial or lateral femoral condyle with and without MAT between 2004 and 2020. Patients were matched 1:1 by age (±5 years), sex (male or female), body mass index (±5), and grouped Kellgren and Lawrence grade (grades 0-1 or 2-4). The minimum follow-up time was 2 years. Radiographic variables (International Cartilage Regeneration & Joint Preservation Society [ICRS] grade and Kellgren and Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery for graft failure or conversion to total knee arthroplasty. Patient-reported, clinical, and radiographic outcomes were compared between groups. In total, 66 patients (33 treated with isolated OCAT, 33 treated with OCAT+MAT; 57.6% male) with a mean age of 26.3 years (range, 18-62 years) were followed for a mean of 5.6 years (minimum, 2 years; range, 24-218 months). The 2 cohorts showed no difference in Kellgren and Lawrence grade postoperatively (P = .59). There was a significantly higher ICRS grade detected at follow-up in the OCAT+MAT group (2.81 ± 1.10) compared with the OCAT group (2.04 ± 0.96) (P < .05). There were no statistically significant differences between the groups regarding reoperation rate (OCAT: n = 6; OCAT+MAT: n = 13; P = .116), time to reoperation (OCAT: 46.67 ± 47.27 months vs OCAT+MAT: 28.08 ± 30.16 months; P = .061), and failure rate (OCAT: n = 4 [12.1%] vs OCAT+MAT: n = 5 [15.2%]; P = .66). In the OCAT+MAT group, an increase of tibial slope by 1° conferred a 1.65-fold increase in the hazard for failure over decreased slope (hazard ratio, 1.65; 95% CI, 1.10-2.50; P < .05). The overall survival rate was 86% at a mean follow-up of 5.6 years. Patient-reported outcome scores were significantly improved at the final follow-up compared with preoperative status. No significant differences were seen between groups with respect to subjective IKDC, Lysholm, Tegner, and KOOS results, except for the KOOS Symptoms subscale score, which was significantly higher in the OCAT+MAT group than in the OCAT group (mean difference, 14.6; P < .05) and did exceed the minimal clinically important difference threshold of 10.7. Midterm results after isolated OCAT and OCAT+MAT show high rates of healing and sustainable subjective improvement of knee function and quality of life. However, it should be noted that the difference in reoperation rate and time to reoperation between the groups is arguably clinically important and that lack of statistical significance may be because of low power. These results imply that isolated OCAT is an efficient joint-preserving treatment that can be combined with MAT in well-selected patients with meniscal insufficiency without negative influence on global clinical outcomes.

Outcome differences by sex in oncology clinical trials

Identifying sex differences in outcomes and toxicity between males and females in oncology clinical trials is important and has also been mandated by National Institutes of Health policies. Here we analyze the Trialtrove database, finding that, strikingly, only 472/89,221 oncology clinical trials (0.5%) had curated post-treatment sex comparisons. Among 288 trials with comparisons of survival, outcome, or response, 16% report males having statistically significant better survival outcome or response, while 42% reported significantly better survival outcome or response for females. The strongest differences are in trials of EGFR inhibitors in lung cancer and rituximab in non-Hodgkin’s lymphoma (both favoring females). Among 44 trials with side effect comparisons, more trials report significantly lesser side effects in males (N = 22) than in females (N = 13). Thus, while statistical comparisons between sexes in oncology trials are rarely reported, important differences in outcome and toxicity exist. These considerable outcome and toxicity differences highlight the need for reporting sex differences more thoroughly going forward.

Trends in opioid toxicities among people with and without opioid use disorder and the impact of the COVID-19 pandemic in Ontario, Canada: A population-based analysis

BackgroundAcross Canada, the COVID-19 pandemic occurred amidst an ongoing drug toxicity crisis. Although elevated rates of substance-related harms have been observed nationally, it remains unknown if the pandemic state of emergency led to disproportionate increases in opioid toxicities among people with opioid use disorder (OUD) compared to those without. MethodsWe conducted a population-based repeated cross-sectional time series analysis of fatal and non-fatal opioid toxicities between January 1, 2014, and December 31, 2021, in Ontario, Canada. We used interventional autoregressive integrated moving average models to examine the impact of the pandemic on monthly rates of opioid toxicities per 100,000 Ontario residents stratified by people with and without OUD. ResultsWe identified 80,296 opioid toxicities of which 53.5 % occurred among people with OUD. Among 52,052 unique individuals, 60.5 % were male and 46.2 % were 25–44 years old. Between January 2014 and December 2021, the rate of opioid toxicities increased from 2.6 to 10.5 per 100,000 (rate ratio [RR]=4.07). The magnitude of this increase differed among people with OUD (0.8 to 7.4 per 100,000; RR=9.35) and without OUD (1.8 to 3.1 per 100,000; RR=1.74). We observed a significant ramp increase in the overall rate of opioid toxicities following the declaration of the pandemic emergency in March 2020 (+0.19 per 100,000 monthly, 95 % CI: 0.029, 0.36, p = 0.021). In a stratified analysis, we found a similar ramp increase among people with OUD (+0.19 per 100,000 monthly, 95 % CI: 0.10, 0.28, p < 0.001); however, this was not observed among people without OUD (p = 0.95). ConclusionsThe rate of opioid toxicities accelerated across Ontario following the pandemic-related state of emergency, with the majority of this increase among people with OUD. The important differences observed among people with OUD compared with those without, highlights the critical need for improved access to harm reduction and treatment interventions among this population.

B cell pathway dual inhibition for systemic lupus erythematosus: a prospective single-arm cohort study of telitacicept.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with B-cell hyperactivity. Telitacicept is a transmembrane activator, calcium modulator, and cyclophilin ligand interactor-Fc fusion protein, which can neutralize both B-cell lymphocyte stimulator and a proliferation-inducing ligand. Patients with active SLE who received telitacicept were prospectively followed at month 1, 3, 6, 9, and 12 after telitacicept initiation. Thirty-seven participants were involved and followed for 6.00 [3.00, 6.00] months. SRI-4 rate at month 6 was 44.7%. The median dosage of prednisone was decreased by 43.8% (from 10 to 5.62mg/d) at month 6. The anti-dsDNA level was significantly decreased, while complement levels were significantly increased at month 6 from baseline. Continuously significant reductions in serum immunoglobin (Ig)G IgA, and IgM levels were also observed. Patients experienced significant decreases in the numbers of total and naive B cells, whereas memory B cells and T cell populations did not change. The number of NK cells was significantly increased during the follow-up. At month 6, 58.3% (14 out of 24) patients experienced improved fatigue accessed by FACIT-Fatigue score exceeding the minimum clinically important difference of 4. Most adverse events were mild, but one each case of severe hypogammaglobulinemia, psychosis with suicidal behavior, and B-cell lymphoma were occurred. In our first prospective real-world study, telitacicept treatment led to a significant clinical and laboratory improvement of disease activity, as well as fatigue amelioration in patients with SLE. Safety profile was favorable overall, but more studies are greatly needed.

Differential cognitive and behavioral development from 6 to 24 months in autism and fragile X syndrome

BackgroundSpecifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants.MethodsThe current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in FXS and FH-ASD infants, compared to FH infants who did not develop ASD (FH-nonASD) and typically developing controls.ResultsInfants with FXS showed delays on a nonverbal composite compared to FH-ASD (as well as FH-nonASD and control) infants as early as 6 months of age. By 12 months an ordinal pattern of scores was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Cognitive level differentially influenced developmental trajectories for FXS and FH-ASD.ConclusionsOur results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups.

Clinical Efficacy and Patient Reported Impacts of Roflumilast Foam 0.3% in Seborrheic Dermatitis: An Analysis of STRATUM Data for Patients Unresponsive or Intolerant to Topical Corticosteroids

Objective. Roflumilast foam 0.3% has demonstrated efficacy and tolerability in a Phase 3 clinical trial of moderate-to-severe seborrheic dermatitis (SD) patients (STRATUM). The aim of this subgroup analysis is to assess the efficacy and patient-reported quality of life (QOL) effects of roflumilast vs vehicle in patients with an inadequate response, intolerance, or contraindication to topical corticosteroids (TCS).&#x0D; Methods: Patients 9 years or older with at least moderate seborrheic dermatitis (Investigator Global Assessment [IGA] ≥ 3) were randomized 2:1 to roflumilast or vehicle for 8 weeks. Patients reporting a history of inadequate response, intolerance, or contraindication to topical corticosteroids (TCS) were included in this subgroup analysis. The primary efficacy endpoint was IGA success (Clear or Almost Clear with at least a 2-grade improvement) at Week 8. QOL was assessed using the Dermatology Life Quality Index (DLQI) for patients aged ≥17 years. QOL endpoints included percentage change from baseline in DLQI score, achievement of a minimal important difference (MID; defined as at least a 4-point reduction in DLQI score), and patients achieving a DLQI score of 0 or 1 by treatment group at weeks 2, 4, and 8. Differences in change from baseline DLQI scores were assessed using the Kruskal-Wallis rank sum test. The Cochran–Mantel–Haenzel test was used to assess differences in the proportion of patients achieving binary endpoints between treatments.&#x0D; Results: 189 patients (129 roflumilast, 60 vehicle) were included in the subgroup analysis. At Week 8, 78.8% of roflumilast patients achieved IGA success vs. 48.3% of vehicle patients (odds ratio [OR] 3.45; 95% confidence interval [CI]: 1.62, 7.36; p&lt;0.001). At each time point, percentage change from baseline in DLQI score was significantly larger for roflumilast-treated patients relative to vehicle (p≤0.001). Treatment with roflumilast significantly increased the odds of achieving an MID in DLQI across all time points (OR: 6.97; 95% confidence interval [CI]: 3.97, 12.24; p&lt;0.001) and achieving a DLQI score of 0 or 1 (OR: 2.46; 95% CI: 1.58, 3.81; p&lt;0.001).&#x0D; Conclusions: Roflumilast foam 0.3% provided significant and meaningful efficacy with improved QOL in patients with moderate-to-severe SD who had a prior history of an inadequate response, intolerance, or contraindication to TCS. Clinical improvement aligned with patient-reported outcomes at all key assessment periods.

Feasibility of transcranial direct current stimulation (tDCS) combined with pelvic floor muscle training (PFMT) in female urinary incontinence: randomized controlled trial

INTRODUCTION: Pelvic floor muscle training (PFMT) is widely regarded as the most conservative and effective non-pharmacological treatment option for women suffering from urinary incontinence (UI). Transcranial direct current stimulation (tDCS) is a non-invasive, non-pharmacological neuromodulation technique that has demonstrated promising results in a variety of medical conditions. However, there has been little research into the feasibility of tDCS as an adjunct therapy to PFMT in improving symptoms in women with UI. OBJECTIVE: To explore the feasibility (recruitment and retention) of tDCS as an adjunct therapy to PFMT to relieve symptoms of female UI. METHODS AND MATERIALS: Eleven female patients were randomly assigned to receive 12 non-consecutive sessions of PFMT combined with 20 minutes (2mA) of anodal (Cz) or sham tDCS for 4 weeks. Feasibility (primary outcome) was assessed through recruitment and retention rates. Secondary outcomes included four domains: (1) urinary leakage, (2) severity of incontinence, (3) impact on quality of life, and (4) symptoms and adverse events. RESULTS: Eleven patients were evaluated, and nine women completed the treatment protocol. The recruitment rate was 100%, and retention was 81.8%. Clinical results showed that anodal tDCS is viable as adjunctive therapy to PFMT protocol and may result in minimal clinically important differences (MCID) in UI symptoms. CONCLUSION: The high rate of recruitment and retention indicates that tDCS in combination with PFMT is a feasible adjunct therapy for female UI treatment. This research supports the recommendation for a full RCT, with prioritization of outcomes required for hypothesis testing.